Cerebellar involvement in metabolic disorders: a pattern-recognition approach

Abstract

Inborn errors of metabolism can affect the cerebellum during development, maturation and later during life. We have established criteria for pattern recognition of cerebellar abnormalities in metabolic disorders. The abnormalities can be divided into four major groups: cerebellar hypoplasia (CH), hyperplasia, cerebellar atrophy (CA), cerebellar white matter abnormalities (WMA) or swelling, and involvement of the dentate nuclei (DN) or cerebellar cortex. CH can be an isolated typical finding, as in adenylsuccinase deficiency, but is also occasionally seen in many other disorders. Differentiation from CH and CA is often difficult, as in carbohydrate deficient glycoprotein syndrome or 2-L-hydroxyglutaric acidaemia. In cases of atrophy the relationship of cerebellar to cerebral atrophy is important. WMA may be diffuse or patchy, frequently predominantly around the DN. Severe swelling of white matter is present during metabolic crisis in maple syrup urine disease. The DN can be affected by metabolite deposition, necrosis, calcification or demyelination. Involvement of cerebellar cortex is seen in infantile neuroaxonal dystrophy. Changes in DN and cerebellar cortex are rather typical and therefore most helpful; additional features should be sought as they are useful in narrowing down the differential diagnosis.

Cranial Ultrasound in Metabolic Disorders Presenting in the Neonatal Period: Characteristic Features and Comparison with MR Imaging

“…Several studies have been performed on brain MR imaging and histologic findings in metabolic disorders presenting during the neonatal period, 3,4,21,24,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] but cUS findings have only been described in individual case reports. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] cUS has the advantage that it is readily available on neonatal units when infants are admitted.…”

Heterozygous Mutations in the ADCK3 Gene in Siblings with Cerebellar Atrophy and Extreme Phenotypic Variability

“…A recently published 10-year retrospective study on childhood onset cerebellar ataxia revealed that in the group with a known genetic diagnosis, mitochondrial disease was the most common cause of cerebellar atrophy (Al-Maawali et al 2012). Other studies on childhood ataxias also confirm that a mitochondrial etiology may be the leading cause of the disease (Ramaekers et al 1997;Steinlin et al 1998;Finsterer 2009;Boddaert et al 2010;Terracciano et al 2012).…”

Branched Chain Amino Acids Induce Apoptosis in Neural Cells without Mitochondrial Membrane Depolarization or CytochromecRelease: Implications for Neurological Impairment Associated with Maple Syrup Urine Disease

“…Acute neurological deterioration in children is often associated with increased plasma and cerebrospinal fluid concentrations of BCAA and BCKA (Riviello et al, 1991;Levin et al, 1993). Magnetic resonance imaging studies in children with MSUD have confirmed both white matter and neuronal injury, including extensive brain edema and pathological changes in the basal ganglia (Brismar et al, 1990;Steinlin et al, 1998). At the histopathological level, deficiencies in myelination of major tracts in the pons and spinal cord, widespread areas of spongy change in the white matter, focal areas of astrocytosis, and binucleated neurons have also been reported (Langenbeck, 1984).…”